The human TOPONOME (HUTO) project

Translating the cellular protein network code (toponome) into efficient therapies

Invention and introduction of the high-throughput robot Imaging Cycler® technology for toponomics allows to microscopically resolve large protein networks consisting of thousands of distinct protein clusters simultaneously at the cell surface, intracellularly, and transcellularly in one experiment distinguishing structure known to be present and at <40 nm distance. High-end Imaging Cycler® robots and specific software have been developed to co-map protein clusters by automatically controlled repetitive cycles of fluorescence protein tagging and imaging thereby overcoming the spectral limitation of wavelengths: the essential condition to identify and decipher the high-dimensional combinatorial molecular structure of protein networks in a cell or in a tissue section. The resulting hierarchical organization of protein clusters uncovers lead proteins, that have been shown to control the integrity of protein networks. Blocking of lead proteins results in a disassembly of the network and loss of function in tumour cells, and similar proofs of principle were obtained by investigating neurological diseases substantiating that Imaging Cycler® toponomic imaging is a new way towards target discovery and predictive biomarkers in chronic diseases. The toponome project, launched by ToposNomos Ltd. is based on international patents. It aims at the deciphering of the protein network code in human cells and tissues in health and disease, by a cooperation of interdisciplinary institutions involving clinicians, molecular biologists, biochemists, computer scientists, and mathematicians.

To make protein network analysis accessible for scientists, the HUTO-project has established high-end Imaging Cycler® and TIS™ robots in the labs of institutions in Germany and UK. The instruments are based upon a 20-year period of continuous technology development.

As a next step and to facilitate access to simultaneous large scale super-resolution protein network imaging in situ/in vivo, the HUTO-project announces the next generation of cost-effective Imaging Cycler® series of microscopes with multiple functionalities in one machine:

Patents: DE 19709348; JP 3739528; USA 6,150,173; EP 0180428